Journal article
Two-dimensional genome-scan identifies novel epistatic loci for essential hypertension
- Abstract:
- It is well established that gene interactions influence common human diseases, but to date linkage studies have been constrained to searching for single genes across the genome. We applied a novel approach to uncover significant gene-gene interactions in a systematic two-dimensional (2D) genome-scan of essential hypertension. The study cohort comprised 2076 affected sib-pairs and 66 affected half-sib-pairs of the British Genetics of HyperTension study. Extensive simulations were used to establish significance thresholds in the context of 2D genome-scans. Our analyses found significant and suggestive evidence for loci on chromosomes 5, 9,11, 15, 16 and 19, which influence hypertension when gene-gene interactions are taken into account (5q13.1 and 11q22.1, two-locus lod score = 5.72; 5q13.1 and 19q12, two-locus lod score = 5.35; 9q22.3 and 15q12, two-locus lod score = 4.80; 16p12.3 and 16q23.1, two-locus lod score= 4.50). For each significant and suggestive pairwise interaction, the two-locus genetic model that best fitted the data was determined. Regions that were not detected using single-locus linkage analysis were identified in the 2D scan as contributing significant epistatic effects. This approach has discovered novel loci for hypertension and offers a unique potential to use existing data to uncover novel regions involved in complex human diseases.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.8MB, Terms of use)
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- Publisher copy:
- 10.1093/hmg/ddl058
Authors
+ Barts and London Charitable Foundation Research Advisory Board
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- Funding agency for:
- Wallace, C
- Grant:
- RAB03/PJ/01
- Publisher:
- Oxford University Press
- Journal:
- Human Molecular Genetics More from this journal
- Volume:
- 15
- Issue:
- 8
- Pages:
- 1365-1374
- Publication date:
- 2006-04-01
- Edition:
- Publisher's version
- DOI:
- EISSN:
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1460-2083
- ISSN:
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0964-6906
- Language:
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English
- Keywords:
- Subjects:
- UUID:
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uuid:3c2b3fd4-4afb-4579-acc8-d9cbda9dc2b4
- Local pid:
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ora:1650
- Deposit date:
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2008-03-14
Terms of use
- Copyright holder:
- Jordana Tzenova Bell et al
- Copyright date:
- 2006
- Notes:
- Originally published as: Tzenova Bell, J. et al. (2006). 'Two-dimensional genome-scan identifies novel epistatic loci for essential hypertension', Human Molecular Genetics, 15(8), 1365-1374. [Available at http://hmg.oxfordjournals.org/]. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact: [email protected]
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